Modulation in the organization of the plasma membrane has been shown to be important in the control of cell proliferation. Our results have demonstrated significant differences between normal and transformed cells in this regard. Further, these results suggest that normal contact inhibited cells modulate membrane organization following cell contact and following mitosis to presumably control the rate of cell growth. Transformed cells fail to respond to contact and mitosis, perhaps accounting for their abnormal growth characteristics. The cellular mechanisms that regulate the organization of the plasma membrane are complex and seem to involve not only changes in the interaction of intrinsic membrane components, but in addition their interaction with cytoplasmic microtubules and microfilaments. These results have resulted from complementary studies employing tissue culture, freeze fracture and electron microscopy, electron spin resonance and various other biological techniques. These data are interpreted to suggest that there are basic differences in the membranes of normal and transformed cells that appear to account for the significantly different growth characteristics of such cells in vitro and in vivo. Studies in progress are designed to explore on a biochemical basis the mechanisms that modulate membrane organization and to attempt to determine whether differences in the organization of microheterogenous domains in the plasma membrane of normal and transformed cells may account for different activities of certain membrane bound enzymes that may affect control of cell proliferation.